1. Field of the Invention
This invention relates to a novel antitumor antibiotic and to its production and recovery.
2. Description of the Prior Art
U.S. Pat. No. 4,107.297 discloses production of an antibiotic AM-2282 by fermentation of Streptomyces staurosporeus nov. sp. ATCC 55006. This antibiotic reportedly has antiinfective and hypotensive activity. AM-2282 was later named staurosporine and its structure is reported in J. Chem. Soc. Chem. Commun. 1978: 800-801, 1978 to be ##STR1##
European Published Patent Application 238,011 discloses an antitumor antibiotic named UCN-01 produced by fermentation of Streptomyces sp. UCN-01 (FERM BP-990) having the structure ##STR2## compound UCN-01 is also described in J. Antibiotics, p. 1782, December 1987.
The antitumor antibiotic named rebeccamycin is disclosed in U.S. Pat. No. 4,552,842 as being produced by fermentation of Nocardia aerocolonigenes ATCC 39243. Rebeccamycin has the structural formula ##STR3## The producing organism has recently been reclassified as Saccharothrix aerocolonigenes (J. Antibiot. 40: 668-678, 1987).
U.S. Pat. No. 4,524,145 discloses the antitumor antibiotic named 4'-deschlororebeccamycin which is produced by fermentation of Saccharothrix aerocolonigenes ATCC 39243. This compound has the structural formula ##STR4##
U.S. patent application Ser. No. 933,428 filed Nov. 21, 1986 discloses a series of antitumor antibiotics of the formula ##STR5## wherein: n is an integer from 1 to 6;
A.sup.6 and A.sup.13 are selected from H and --(CH.sub.2)NR.sup.1 R.sup.2 of A.sup.6 and A.sup.13 is --(CH.sub.2).sub.n --NR.sup.1 R.sup.2 ; PA1 CHCl.sub.3 --CH.sub.3 OH (9:1 v/v): 0.42. THF: 0 20. PA1 Whatman MKC.sub.18 ; PA1 0.1 M NH.sub.4 OAc-THF (1:1 v/v): 0.25.
R.sup.1 and R.sup.2, independently are selected from hydrogen unsubstituted and substituted C.sub.1 -C.sub.6 alkyl, aralkyl having 1 to 3 carbons in the alkyl moiety and unsubstituted phenyl or phenyl substituted with 1 to 3 alkyl, alkoxy hydroxy, halo, carboxyl, alkoxycarbonyl, and amino and mono- and di-lower-alkylamino groups in the aryl moiety, and aryl selected from unsubstituted phenyl and phenyl substituted with 1 to 3 alkyl, alkoxy, hydroxy, halo, amino, mono- and dialkylamino, nitro, carboxyl, alkoxycarbonyl, and cyano groups provided that both R.sup.1 and R.sup.2 are not each aryl and, when taken together, R.sup.1 and R.sup.2 may be selected from --(CH.sub.2).sub.4 -- and (CH.sub.2).sub.2 --R.sup.3 --(CH.sub.2).sub.2 -- to form a 5- or 6-membered ring together with the N-atom wherein R.sup.3 is selected from CH.sub.2, NH, O and S;
X is selected from H, F, Cl, Br, C.sub.1 -C.sub.3 alkyl, OH, carboxyl, alkoxycarbonyl and alkoxy wherein the alkyl moiety is C.sub.1 -C.sub.3 alkyl, benzyloxy, amino, and mono- and dialkylamino; and
R.sup.4 is selected from H and CH.sub.3 ; and pharmaceutically acceptable acid addition and base salts thereof.
European Published Patent Application 175,284 discloses four antitumor antibiotics designated AT2433A1, AT2433A2, AT2433B1 and AT2433B2 produced by fermentation of Actinomadura melliaura ATCC 39691. These compounds have the structural formulae ##STR6## wherein X is H or Cl and R is H or CH.sub.3.
PCT Application W088/07045 discloses derivatives of the compound K252 which are reported to have in vitro antitumor activity against certain cell lines. Among the compounds disclosed are certain 7-oxo derivatives of K252 which appear as compounds 65-76 on page 44.